Circular RNAs in the pathogenesis of cancer: are the interactions with miRNAs relevant?

The goal of this thesis was to investigate the role of circRNAs in B-cell lymphoma and breast cancer. We focused on the characterization of their expression patterns, functional mechanisms, and regulatory roles. In the first part, we conducted RNA sequencing to characterize the circRNA landscape of three main B-cell lymphoma subtypes and normal B-cells. This was followed by more in-depth studies of the roles of circPVT1 and circZDHHC11 in B-cell lymphoma. CircPVT1 and the linear PVT1 transcripts showed opposite differential expression patterns and both supported cell growth. In contrast to other cancers, we showed that the effect on growth was independent of their ability to bind miRNAs. CircZDHHC11 was strongly enriched in the AGO2-IP fraction upon miR-150 overexpression and supported the growth of B-cell lymphoma. However, its growth-supporting effect was independent of its ability to bind miR-150. In the second part, we investigated the role of circ-NOL10 in breast cancer. Circ-NOL10 was selected based on its most pronounced downregulation in triple-negative breast cancer (TNBC) compared to control tissue. Upon binding of MTDH and CASC3, circ-NOL10 levels were strongly reduced, resulting in the release of miR-149-5p, miR-330-3p, and miR-452-5p. These miRNAs subsequently targeted PDCD4 and this promoted progression of breast cancer. Overall, our study extends current knowledge of circRNAs and highlights specific functions of selected circRNAs in B-cell lymphoma and breast cancer.